Our studies aim at elucidating the molecular mechanism involved in the regulation of gene expression in bacteria and in animal cells. The systems under investigation are the regulation of the lactose operon of E. coli and the mechanisms of killing of lymphoid cell lines by glucocorticoids. (1) The lactose operon: The isolation and characterization in vitro of new types of mutants altered either in the structure of the repressor or of the operator is being pursued. (2) Glucocorticoid regulation: We will examine the effect of the amount of glucocorticoid receptor on the sensitivity of lymphoid cell lines. We will also attempt to isolate new types of glucocorticoid resistant variants. We will initiate biochemical studies of the glucocorticoid receptor--i.e., examine its subunit structure and begin its purification.